In recent years it has become apparent that the detection and measurement of tumor-specific or tumor-associated antigens in the serum of cancer patients represents a new and exciting approach for the immunodiagnosis of human malignancy. The experience in the last few years with radioimmunoassays specific for three tumor associated carcinofetal antigens, alpha-1-fetoprotein (AFP), beta-fetoprotein or ferritin, and carcinoembryonic antigen (CEA), have demonstrated these markers to be of definite, although limited, diagnostic or prognostic usefulness. In addition to these carcinofetal proteins, there is increasing evidence that sera from malignant patients contain immune complexes which may contain new membrane or tumor cell associated antigens. Therefore, our overall objectives in the next grant period will be (1) to measure these immune complexes by several techniques in the sera of patients with gastrointestinal malignancies and relate the level of immune complexes to the degree of disease; (2) to isolate these immune complexes, characterize their components and compare the components of the complexes in different GI malignancies; and (3) to develop radioimmunoassays to detect these newly shed neoantigens in the earlier stage of disease.